Abstract:
:We have examined the kinetics of the effects of inhibitors of the Na+/H(+)-antiporter (dimethylamiloride) and the vacuolar H(+)-ATPase (bafilomycin A1) on bone resorption by disaggregated rat osteoclasts in the bone slice assay. Bafilomycin A1 (100 nM) inhibited resorption by approximately 95%, 75%, 80% and 60% respectively, when added at t = 0, 1, 3 or 6 hr after osteoclast adherence to bone slices, during a 24 hr culture period. The incomplete inhibition by bafilomycin A1 when added after the start of incubation was presumably accounted for by resorption that had occurred prior to addition of the compound. Dimethylamiloride (100 microM) inhibited bone resorption by 80% and 65% when added at t = 0 or 1 hr after osteoclast adherence, but was without effect when added at t = 3 or 6 hr. In addition, dimethylamiloride but not bafilomycin A1 strongly inhibited osteoclast cytoplasmic spreading. The results indicate that Na+/H(+)-antiporter activity is essential for controlling intracellular pH during early activation events stimulated by the adherence of osteoclasts to mineralized bone surfaces, which lead to cytoskeletal activation, cell spreading and bone resorption.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Hall TJ,Schaeublin M,Chambers TJdoi
10.1016/0006-291x(92)91344-psubject
Has Abstractpub_date
1992-11-16 00:00:00pages
1097-103issue
3eissn
0006-291Xissn
1090-2104pii
0006-291X(92)91344-Pjournal_volume
188pub_type
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